Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant

Abstract

Isolated aldosterone synthase deficiency may result in life-threatening salt-wasting and failure to thrive. The condition involves hyperkalemia accompanying hyponatremia. Two types of aldosterone synthase deficiency may be observed depending on hormone levels: corticosterone methyl oxidase type 1 (CMO 1) and CMO 2. Herein, we describe a Turkish infant patient with aldosterone synthase deficiency who presented with failure to thrive and salt wasting but with normal potassium levels. Urinary steroid characteristics were compatible with CMO I deficiency. Diagnosis of aldosterone synthase deficiency was confirmed by mutational analysis of the CYP11B2 gene which identified the patient as homozygous for two mutations: c.788T>A (p.Ile263Asn) and c.1157T>C (p.Val386Ala). Family genetic study revealed that the mother was heterozygous for c.788T>A and homozygous for c.1157T>C and the father was heterozygous for both c.788T>A and c.1157T>C. To the best of our knowledge, this is only the second Turkish case with a confirmed molecular basis of type 1 aldosterone synthase deficiency. This case is also significant in showing that spot urinary steroid analysis can assist with the diagnosis and that hyperkalemia is not necessarily part of the disease.

Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance

“…Previously, only 2 genetically confirmed Turkish patients were reported in two different articles (p.G435S and p.I263N mutations). 15,20 In this study, both patients 1 and 2 are homozygous for p.I263N, the same variant reported by Ustyol et al 20 There has not been a reported functional study of this variant. Nevertheless, with the addition of these 2 unrelated patients, it is clear that the isoleucine-to-asparagine substitution at codon 263 in CYP11B2 is disease causing.…”

“…Three of the IHA patients in this study whose initial endocrinological evaluation showed hyperreninaemic hypoaldosteronism had been successfully treated with fludrocortisone. Previously, only 2 genetically confirmed Turkish patients were reported in two different articles (p.G435S and p.I263N mutations) . In this study, both patients 1 and 2 are homozygous for p.I263N, the same variant reported by Ustyol et al .…”

“…Previously, only 2 genetically confirmed Turkish patients were reported in two different articles (p.G435S and p.I263N mutations) . In this study, both patients 1 and 2 are homozygous for p.I263N, the same variant reported by Ustyol et al . There has not been a reported functional study of this variant.…”

Congenital hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency type I in a Portuguese patient – Case report and review of literature

“…Typically, the disease manifests in the first weeks of life with nausea, vomiting, feeding problems and failure to thrive in the neonatal period. Isolated aldosterone deficiency is associated with neonatal salt-wasting syndrome resulting in hyponatremia, hyperkalaemia, metabolic acidosis and marked elevated renin with low or unappropriated normal aldosterone levels (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Usually, clinical severity improves with age and patients are frequently asymptomatic during adulthood despite not having mineralocorticoid therapy (16).…”

“…Most of the cases reported in the literature are from Iranian Jewish patients (5,16,17), but cases from Turkey (14,18) , Japan (7,8) and Israel (9,19) have also been described. To our knowledge, there has been no previous report of Portuguese cases of AS deficiency, especially with confirmed genetic analysis.…”